New Hope for Sleep Apnea Patients May Be Coming

The cardiac autonomic nervous system is a potential therapeutic target for atrial fibrillation

Atrial fibrillation (AF) is currently the most common type of treated heart arrhythmia. By 2030, the Centers for Disease Control and Prevention (CDC) estimates that 12.1 million people in the United States will have AF. The CDC has also noted that more than 454,000 hospitalizations occur each year in the United States where AF is the primary diagnosis. Specifically, in 2019, AF was specified in 183,321 death certificates and was the underlying cause of death in 26,000 of those. Interestingly, a close association exists between AF and both types of sleep apnea – obstructive sleep apnea (OSA) and central sleep apnea. In sleep apnea, there is discontinuance or decrease in breathing during sleep for at least 10 seconds, which causes oxygen desaturation. OSA is caused by partial or complete collapse of the upper airways whereas the less common central sleep apnea is caused due to absence or depletion of respiratory efforts. Like AF, sleep apnea also has a high prevalence in the United States. Moreover, sleep apnea is widespread among patients with AF. Mechanistically how these two are related is unclear – although research suggests dysfunction of the cardiac autonomic nervous system (ANS) may play a plausible role. In a review study published in the Methodist DeBakey Cardiovascular Journal in 2021, Miguel Valderrábano, MD, FACC, professor of Cardiology and the Lois and Carl Davis Centennial Chair of the DeBakey Heart & Vascular Center at Houston Methodist detailed the key points of the role of ANS in sleep apnea-induced AF. Additionally, he suggested the cardiac afferents of the cardiac ANS as a therapeutic target for decreasing AF in patients suffering from sleep apnea.

Miguel Valderrábano, MD, FACC

Sleep apnea is highly associated with atrial fibrillation. The cardiac autonomic nervous system plays an important role in this association, and studies have shown that different components of this system could potentially be therapeutically targeted to decrease atrial fibrillation inducibility in patients with obstructive sleep apnea. Cardiac afferents are a crucial component of the cardiac autonomic nervous system and have therapeutic potential in reducing atrial fibrillation in those with sleep apnea.

Miguel Valderrábano, MD, FACC

Professor of Cardiology and the Lois and Carl Davis Centennial Chair of the DeBakey Heart & Vascular Center at Houston Methodist

Both sleep apnea and AF are significant contributors to cardiovascular diseases – leading to an overall increase in mortality, morbidity and escalating healthcare burdens. Sleep apnea enhances the risk of hypertension, coronary artery disease, congestive heart failure, stroke, diabetes and heart arrhythmias. On the other hand, AF enhances the risk of stroke, heart failure and dementia. Cardiac ANS, which regulates the cardiovascular system, functions optimally when there is a precise balance between the modulations in the parasympathetic and sympathetic branches. Efficient cardiac ANS function is linked to a diminished risk of cardiovascular complications. Conversely, an imbalance in cardiac ANS activity can lead to a dysregulation of the heart rate and blood pressure as well as cardiovascular complexities and diabetes.

Sleep apnea induces acidosis, hypoxia, hypercarbia and increased blood pressure, which trigger an increase in cardiac ANS activity. Increased cardiac ANS activity leads to hemodynamic and electrophysiological shifts which actuate AF susceptibility. Studies that recorded intrinsic and extrinsic cardiac ANS activity in response to sleep apnea have demonstrated a mechanistic association between the cardiac ANS and sleep apnea-induced AF. Cardiac ANS is thought to mediate the electrophysiological responses of the atrial myocardium to apnea and thus, the cardiac afferents are a potential therapeutic target. According to Valderrábano, “Sleep apnea is highly associated with atrial fibrillation. The cardiac autonomic nervous system plays an important role in this association, and studies have shown that different components of this system could potentially be therapeutically targeted to decrease atrial fibrillation inducibility in patients with obstructive sleep apnea. Cardiac afferents are a crucial component of the cardiac autonomic nervous system and have therapeutic potential in reducing atrial fibrillation in those with sleep apnea.”Sleep apnea is a risk factor for the initiation, maintenance and recurrence of AF – although other risk factors such as age (over 60 years), presence of heart disease, hypertension and obesity also exist. Currently, treatments geared towards reducing the incidence or recurrence of AF mainly involve treatments that target sleep apnea. For instance, continuous positive airway pressure treatments improve patient-reported symptoms of sleep apnea such as snoring, daytime fatigue, restlessness during sleep and frequent nighttime awakenings. But these treatments also improve vascular parameters, AF symptoms and cardiovascular measures such as blood pressure. The intersection of sleep apnea and AF and how the cardiac ANS is mechanistically related to this nexus is critical to understand in order to develop better strategies for therapeutic interventions. Further studies and randomized clinical trials need to be conducted to discern if other components of the cardiac ANS, such as parasympathetic nerves, sympathetic nerves, epicardial ganglionated plexi or sensory afferents can be targeted for more effective management of AF in patients with sleep apnea. Collaborations between cardiologists, sleep medicine experts and clinical trial communities are imperative towards this end.

Liliana Tavares, Adi Lador, Miguel Valderrábano. Sleep Apnea and Atrial Fibrillation: Role of the Cardiac Autonomic Nervous System. Methodist Debakey Cardiovasc J. 2021 Apr 5;17(1):49-52. doi: 10.14797/ZYUT2951.

Abanti Chattopadhyay, PhD

October 2022

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